Heteropodatoxin

Heteropodatoxins are peptide toxins from the venom of the giant crab spider "Heteropoda venatoria", which block Kv4.2 voltage-gated potassium channels.

Source

Heteropodatoxins are purified from the venom of the giant crab spider, "Heteropoda venatoria" Harv |Sanguinetti|1997|.

Chemistry

Heteropodatoxins contain an Inhibitory Cystin Knot (ICK) motif, which consist of a compact disulfide-bonded core, from which four loops emerge Harv |Bernard|2000|. There are three different heteropodatoxins Harv |Sanguinetti|1997|:
* heteropodatoxin-1, also known as Toxin AU3/KJ5 or HpTx1
* heteropodatoxin-2, also known as Toxin KJ6 or HpTx2
* heteropodatoxin-3, also known as Toxin AU5C/KJ7 or HpTx3

These three toxins are structurally similar peptides of 29-32 amino acids Harv |Sanguinetti|1997|. They show sequence similarity to Hanatoxins, which can be isolated from the venom of the Chilean rose tarantula Grammostola rosea Harv |Sanguinetti|1997|.

Target

Heteropodatoxins block A-type, transient voltage-gated potassium channels. All three toxins have been shown to block the potassium channel Kv4.2 Harv |Sanguinetti|1997|. Recombinant heteropodatoxin-2 blocks the potassium channels Kv4.1, Kv4.2 and Kv4.3, but not Kv1.4, Kv2.1, or Kv3.4 Harv |Zarayskiy|2005|.

Mode of action

Heterpodatoxin-2 most likely acts as a gating modifier of the Kv4.2 channels Harv |Zarayskiy|2005|. It shifts the voltage dependence of the activation and the inactivation of the Kv4.3 potassium channel to more positive values. As a result, in the presence of the toxin this channel has a higher probability of being inactivated and a larger depolarization is needed to open the channel. However, heterpodatoxin-2 did not affect the voltage dependence of the Kv4.1 channel, suggesting that the precise mechanism of block remains to be elucidated Harv |Zarayskiy|2005| and a role as a pore blocker cannot be excluded Harv |Bernard|2000|. The voltage dependence of Kv4.2 block varies among the three different heteropodatoxins. It is less voltage dependent for HpTx1 than for HpTx2 or HpTx3 Harv |Sanguinetti|1997|.

Toxicity

The giant crab spider can cause a locally painful bite http://creatures.ifas.ufl.edu/urban/spiders/giant_crab_spider.htm.

References